Coadministration of disulfiram and lorazepam in the treatment of alcohol dependence and co-occurring anxiety disorder: an open-label pilot study

Abstract

Background Anxiety is common among persons with alcohol use disorder during early abstinence from alcohol. Although benzodiazepines are effective for short-term treatment of anxiety, they are rarely used beyond acute detoxification due to concerns about misuse or interactions with alcohol. Objectives We conducted an open-label trial to explore the effects of coadministering lorazepam and disulfiram to alcohol dependent patients with anxiety disorder symptoms. The rationale for this model is to minimize the risks of the benzodiazepine, while also potentially enhancing adherence to disulfiram. Methods Forty-one participants with DSM-IV alcohol dependence who also met syndromal criteria for anxiety disorder with or without co-occurring major depressive syndrome initiated treatment with lorazepam (starting dose 0.5 mg three times daily) and disulfiram (starting dose 500mg three times weekly). Participants received 16 weeks of monitored pharmacotherapy with manualized medical management. Results Adherence to treatment decreased steadily with time (85.4% at 4 weeks, 36.6% at 16 weeks). Participants showed significant increases in percent abstinent days during treatment and at 24 week follow-up. Large reductions in anxiety, depression, and craving were observed during treatment, and improvement remained significant at 24 weeks. Duration of adherence with disulfiram strongly predicted abstinence at 16 weeks. There was no evidence of misuse of lorazepam or dose escalation during the study. Conclusion Lorazepam can be safely used for short-term treatment of anxiety in combination with disulfiram treatment of alcohol use disorder. Controlled trials are necessary to determine the effects of lorazepam on anxiety, retention in treatment, and drinking in this context.

Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms—A bayesian network meta‐analysis

“…Findings from a recent open‐label trial including 41 AUD patients were partly consistent with ours. It found that disulfiram plus lorazepam could significantly increase the percent abstinent days and reduce depressive symptoms 96 . However, in our study, disulfiram showed no benefit to depressive symptoms compared to controls, indicating the need for combination with medication specifically targeting depressive symptoms.…”

“…As one of the earliest approval medications for alcoholism, in our study, disulfiram was demonstrated to be the most efficacious 96 However, in our study, disulfiram showed no benefit to depressive symptoms compared to controls, indicating the need for combination with medication specifically targeting depressive symptoms. By extendedly blocking the acetaldehyde dehydrogenase, disulfiram could trigger uncomfortable "Antabuse" reactions such as tachycardia, flushing, and nausea after drinking, which gradually established the aversion to alcohol and finally achieve the aim of quitting drinking.…”

Disulfiram Produces Potent Anxiolytic-Like Effects Without Benzodiazepine Anxiolytics-Related Adverse Effects in Mice

“…A previous clinical study indicated that DSF was more effective than a placebo and as effective as the benzodiazepine anxiolytic chlordiazepoxide at reducing anxiety in alcoholic outpatients ( Rosenberg, 1974 ). Another study indicated that coadministration of DSF and lorazepam to alcoholic patients with co-occurring anxiety disorder largely reduced anxiety, depression, and cravings ( Bogenschutz et al, 2016 ). However, other investigations reported no statistically significant anxiolytic effects attributable to DSF in alcoholics ( Snyder and Keeler, 1981 ; Goyer et al, 1984 ).…”

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

“…The medications recommended to treat alcohol use disorders (AUD) in Brazil are the same as those approved by the Food and Drug Administration (FDA): disulfiraminhibits acetaldehyde dehydrogenase; naltrexone -blocks µ-opioid receptors; and acamprosate -blocks N-methyl-D aspartate glutaminergic receptors (Williams, 2005;Bogenschutz et al, 2016;Walker et al, 2019;Jorgensen, Pedersen, Tonnesen, 2011;Campana et al, 2012). These medications are recommended to control the desire and / or urge to drink, in addition to psychosocial monitoring (Campana et al, 2012).…”